We propose a Phase 1 pilot study to set the stage for a Phase 3 study of thyroid supplementation in infants born prior to 28 weeks of gestation to assess whether such treatment improves long-term outcomes, specifically IQ and risk of disabling cerebral palsy. The purpose of the pilot study is to establish the dosing schedules needed to achieve the optimum plasma hormone targets in the neonatal period, without increasing measures of neonatal morbidity, mortality or physiological dysfunction. A particular goal is to avoid suppression of thyroid stimulating hormone from administration of thyroid hormone. We also aim to demonstrate cooperation among an international consortium of five participating institutions before initiating a trial to involve about 20 study sites. Six groups of 24 infants each will receive saline control, iodine supplementation, or any of four combinations of thyroid hormone, varying in type (thyroxine combined with tri-iodothyronine), dosage (4 or 8 pg/kg/day) and route of administration (bolus or continuous). Enrollment will take place in three sites: Westchester Medical Center-New York Medical College, Valhalla, NY; Emma Children's Hospital-Academic Medical Center, Amsterdam, the Netherlands; and Hospital La Paz-Autonomous University of Madrid, Spain. Measures of thyroid hormone and iodine status will be obtained at specific times on study subjects and their mothers, and cortisol levels in infants. Experienced laboratories in California and Spain will be employed for assessing hormones and iodine levels respectively. Several thyroid-related physiological measures will be prospectively recorded from medical records. A patient safety-monitoring plan has been developed. Data will be entered using a web-based system and analyzed at the data coordination center of Michigan State University. As soon as clarity is obtained on the optimum mode of achieving euthyroidemia in the study population, the research team will apply for a subsequent Planning Grant to develop the protocols and instruments for the eventual full-scale multicenter trial.